A number of chemical agents known to disrupt the organization of microtubule structures outside of the CNS exhibit striking biological effects within the central nervous system, and it is likely that these effects are mediated by a molecular action on microtubules. The main objective of this research project is to investigate the interactions of drugs with brain microtubule proteins. Research methods will involve study of the chemical interactions of isotopically labeled drugs with microtubule proteins from brain, and the biochemical characterization of the microtubule subunit proteins. The specific aims are to (1) broaden our knowledge of the biochemistry and biological function of microtubules of the central nervous system; (2) elucidate the precise molecular mechanisms of action of substances which affect brain microtubules; and (3) gather information concerning the biochemical similarities and differences of microtubules in brain compared with those from other sources.